Novel Engineered Toxin Body Targeting CTLA-4 Shows Potential Among Select Advanced Solid Tumors

According to results from a phase 1 trial, an engineered toxin body (ETB) which targets the CTLA-4–expression regulatory T-cells in the tumor microenvironment for destruction, MT-8421, demonstrated an acceptable safety profile with no dose-limiting toxicities and the maximum tolerated dose was not reached.

These results were first presented by Justin T Moyers, MD, Cedars-Sinai, Los Angeles, California, at the 2025 ESMO Targeted Anticancer Therapies Congress in Paris, France.

This open-label, multicenter phase 1 study enrolled 15 patients with advanced solid tumors. There were 8 patients with melanoma, 2 with non-small cell lung cancer (NSCLC), 2 with head and neck squamous cell carcinoma (HNSCC), and 1 each of renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and cervical cancer. Most patients had received prior anti–PD-1 therapy and anti-CTLA4. Patients were treated across 3 dose levels: 32 μg/kg, 48 μg/kg, and 72 μg/kg, administered intravenously over 30 minutes on days 1, 8, 15, and 22 of 28-day cycles. The primary end points included adverse events, dose-limiting toxicities, and maximum tolerated dose. Secondary end points included objective response rate.

There were no dose-limited toxicities observed during the study. All treatment-related adverse events were grade 1/2, including infusion reactions, fatigue, pruritus, chills, and rash. All grade 3 treatment-emergent adverse events were not related to the study treatment, and there were no grade 4/5 adverse events reported. 

While there were no objective responses among the 9 evaluable patients, there were 3 patients who achieved stable disease as best objective response (melanoma, n= 2; HNSCC, n = 1), for a disease control rate of 22%. There was 1 patient with melanoma, who had received prior dual checkpoint therapy, who experienced a non-target lesion regression and ctDNA clearance for >9 months.

According to Dr Moyers, MT-8421 showed an acceptable safety profile with no dose-limiting toxicities or drug-related grade ≥3 toxicities and the maximum tolerated dose was not reached. He concluded, “Further evaluation of CTLA4-targeting ETBs is warranted.”

Source:

Moyers JT. First-in-human, dose escalation of MT-8421: A novel engineered toxin body (ETB) targeting CTLA-4, in patients with select advanced solid tumors. Presented at ESMO Targeted Anticancer Therapies Congress 2025. March 3-5, 2025; Paris, France. Abstract: 10O.